细胞密度调节结肠癌细胞整合素ανβ6表达——癌细胞永生化侵袭生长机制的研究

Cell density mediates integrin ανβ6 expression in colon cancer cells——A mechanism by which cancer cells sustain a self-perpetuating growth manner

目的:探讨细胞高密度和细胞挤压状态对结肠癌细胞表面整合素ανβ6表达的影响效果,探讨结肠癌细胞永生化侵袭生长的机制。方法:用流式细胞术检测结肠癌细胞系WiDr、SW480细胞株和人正常角质细胞系HaCaT细胞株,在高低密度培养条件下各细胞表面的ανβ6表达水平;同时将100例结肠癌标本高细胞密度易侵袭的肿瘤边缘部分及低细胞密度的肿瘤中心部分制作成200点的组织芯片,用免疫组织化学方法检测整合素ανβ6在结肠癌不同部位的分布和表达差异。结果:表达ανβ6的结肠癌细胞出现细胞密度依赖的ανβ6表达增加,而缺乏ανβ6表达的癌细胞和正常角质细胞系HaCaT细胞在高低密度培养条件下ανβ6表达没有改变。组织芯片免疫组织化学检查结果显示结肠癌ανβ6阳性表达率为38%,在癌细胞密度高、细胞拥挤的肿瘤边缘部分ανβ6高表达占73.7%(28/38),且ανβ6密布于肿瘤侵袭边缘,而肿瘤中央组织以ανβ6低表达为主,高表达仅占28.9%(11/38)。结论:细胞高密度和细胞挤压状态诱导癌细胞ανβ6表达可能是构成结肠癌细胞永生化侵袭性生长的基础。

Objectice To detect the effect of cell density on integnn αvβ6 expression and the mechanism by which cancer cells sustain invasive growth via a self-perpetuating manner in colon cancer progression, Methods Flow cytometry was applied to analyze αvβ6 expression in human colon cancer line, WiDr, SW480 cells and the normal human keratinocyte cell line, and HaCaT cells, respectively, at low and high cell density culture respectively. An immunohistochemical study of integrin αvβ6 was performed on tissue microarrays of 200 points/100 cases malignant colon specimens. Two cores were taken from each sample, one obtained from invasive tumor portions （tumor margin, especially cell crowding margin at high cell density）, the other obtained from non-invasive portions （centre tumor foci at low cell density）. High cell density evidently enhanced integrin αvβ6 expression only for WiDr cells expressing αvβ6 compared with low density, but no increase was observed for both SW480 cells which lack αvβ6 and HaCaT cells. The αvβ6 expressive rate on immunoreactivity was 38% （38 in 100 cases）. High positive expression for αvβ6 on immunoreactivity was observed in invasive tumor edged portions in 73.7% （28/38） cases. In non-invasive centre tumor portions, low αvβ6 positive expressive was frequently observed and high αvβ6 expressive only seen in 28,9% （11/38） cases. Cosschsion Cell crowding and dense induced integrin αvβ6 expression, which provided the basis for a self-perpetuating system of tumor invasive infiltrating growth in colon cancer progression.